Prostate Cell News Volume 9.47 | Dec 7 2018

TOP STORY

Targeting FOXA1-Mediated Repression of TGF-β Signaling Suppresses Castration-Resistant Prostate Cancer Progression

FOXA1 down-regulation induced TGF-β signaling, epithelial-mesenchymal transition, and cell motility, which was effectively blocked by TGF-β receptor I inhibitor galunisertib (LY2157299). Combinatorial LY2157299 treatment sensitized prostate cells to enzalutamide, leading to synergistic effects in inhibiting cell invasion in vitro and xenograft castration resistant prostate cancer tumor growth and metastasis in vivo. [J Clin Invest] Abstract | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

NSD2 Is a Conserved Driver of Metastatic Prostate Cancer Progression

Scientists elucidated cell-intrinsic drivers of metastatic prostate cancer progression through analyses of genetically engineered mouse models and correlative studies of human prostate cancer. In particular, nuclear receptor binding SET Domain Protein 2 (NSD2) was robustly expressed in lethal prostate cancer in humans, while its silencing inhibited metastasis of mouse allografts in vivo. [Nat Commun] Full Article | Press Release

Dysregulation of p53-RBM25-Mediated circAMOTL1L Biogenesis Contributes to Prostate Cancer Progression through the circAMOTL1L-miR-193a-5p-Pcdha Pathway

The authors showed that a amotl1-derived circRNA, termed circAMOTL1L, was downregulated in human prostate cancer (PCa), and that decreased circAMOTL1L facilitated PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. [Oncogene] Full Article

Genome-Wide CRISPR Screens Reveal Synthetic Lethality of RNASEH2 Deficiency and ATR Inhibition

Scientists demonstrated that RNASEH2 deficiency is synthetic lethal with ataxia telangiectasia mutated and RAD3 related (ATR) inhibition both in vitro and in vivo. RNASEH2-deficient cells exhibited elevated levels of DNA damage and, when treated with AZD6738, underwent apoptosis or senescence. [Oncogene] Abstract

PDCD4 Is an Androgen-Repressed Tumor Suppressor That Regulates Prostate Cancer Growth and Castration Resistance

Androgen treatment suppressed PDCD4 expression in a dose-responsive and miR-21-dependent manner. PDCD4 knockdown enhanced androgen-dependent cell proliferation and cell cycle progression, inhibited apoptosis, and was sufficient to drive androgen-independent growth. [Mol Cancer Res] Abstract

Development and Characterization of a Spontaneously Metastatic Patient-Derived Xenograft Model of Human Prostate Cancer

Researchers describe the establishment and characterization of an AR⁺, PSMA⁺, ERG⁺, PTEN^−/−, CHD1^+/− patient-derived xenograft model termed ‘C5’, which has been developed from a 60 years old patient suffering from castration-resistant prostate cancer. [Sci Rep] Full Article

Characterization of an In Vitro Model to Study the Possible Role of Polyomavirus BK in Prostate Cancer

Normal epithelial prostate RWPE-1 cells and PCa PC-3 cells were infected with polyomavirus BK for 21 days. Cell proliferation, cytokine production, adhesion, invasion ability, and epithelial-to-mesenchymal transition markers were analyzed. [J Cell Physiol] Abstract

BCAR4 Activates GLI2 Signaling in Prostate Cancer to Contribute to Castration Resistance

Overexpression of breast-cancer anti-estrogen resistance 4 (BCAR4) in PC346 cells increased cell growth and migration, but turned the cells insensitive to androgen. On the other hand, growth and migration of androgen receptor-negative DU145 cells are insensitive to androgen, while depletion of BCAR4 in DU145 cells not only decreased cell growth, but also turned the cells sensitive again to androgen. [Aging (Albany NY)] Full Article

KLF2 Inhibits the Migration and Invasion of Prostate Cancer Cells by Downregulating MMP2

Scientists identified that Kruppel-like factor 2 (KLF2) was downregulated both in prostate cancer (PCa) clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2. [Am J Mens Health] Full Article

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Oligometastatic Prostate Cancer: Reality or Figment of Imagination

In the long term, refinement of the oligometastatic case definition likely will require biologic risk-stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis-directed therapy, future efforts should focus on conducting high-quality, prospective trials with much-needed molecular correlative studies. [Cancer] Full Article

Forkhead Box O4 Transcription Factor in Human Neoplasms: Cannot Afford to Lose the Novel Suppressor

The authors present the clinical and pathological significance of forkhead box O4 (FOXO4) in human cancer. Additionally, the potential clinical applications of future FOXO4 research are discussed. [J Cell Physiol] Abstract

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Genomic Health and Biocartis Expand Collaboration to Urology with the Development of an Idylla^™ Oncotype DX^® Genomic Prostate Score^® Test

Genomic Health, Inc. announced they have expanded their exclusive collaboration into the field of urology with the development of an in vitro diagnostic version of the Oncotype DX^® Genomic Prostate Score^® test on Biocartis’ Idylla^™ platform and potentially additional cancer tests that can be performed locally by laboratory partners and in hospitals around the world. [Genomic Health, Inc.] Press Release

Progenics Doses First Patient in Pivotal Phase III Study of PyL, PSMA PET Imaging Agent, for the Detection of Prostate Cancer

Progenics Pharmaceuticals, Inc. announced that the first patient has been dosed in the company’s Phase III CONDOR study evaluating the diagnostic performance and clinical impact of PyLTM in men with biochemical recurrence of prostate cancer. [Progenics Pharmaceuticals, Inc.] Press Release

Combination Tablet Treats BPH Symptoms; Shrinks Prostate and Prevents BPH Progression

Veru Inc. announced that the company has dosed its first patient for its bioequivalence study of Tadalafil and Finasteride combination tablet for benign prostatic hyperplasia (BPH). The bioequivalence study will enroll 36 patients and will be completed in approximately four weeks. [Veru Inc.] Press Release

Site Visit Planned for December 19, 2018 to Initiate Phase II Trial of ProscaVax for Early-Stage Prostate Cancer

OncBioMune Pharmaceuticals, Inc. provided an update on the Phase II clinical trial of ProscaVax being hosted at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard University. OncBioMune has confirmed that a site visit is scheduled for December 19, 2018. This is the check-off meeting before beginning enrollment in the clinical trial, which is expected to transpire in the coming weeks. [OncBioMune Pharmaceuticals Inc.] Press Release

Research Funders Make Secretive Overseas Investments: Report

An investigation by Science reveals that charities’ investments support activities opposed to their own missions, such as human health and environmental protection. [The Scientist] Editorial

China Backs Bold Plan to Tear Down Journal Paywalls

In a huge boost to the open-access movement, librarians and funders in China have said that they intend to make results of publicly funded research free to read immediately on publication. The move includes a pledge of support for Plan S, a bold initiative launched in September by a group of European funders to ensure that, by 2020, their scientists make papers immediately open. [Nature News] Editorial

NEW Genitourinay Cancers Symposium
February 14-16, 2019
San Francisco, California, United States

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NEW Postdoctoral Associate – Prostate Cancer (Baylor College of Medicine)

Tenure-Track/Tenured Faculty Position – Cancer Biology (University of Chicago)

Assistant Professor – Department of Integrative Biology & Pharmacology (University of Texas Health Science Center at Houston)

Faculty & Leadership Positions- Cancer-Focused Target & Drug Discovery (The University of New Mexico)

Postdoctoral Associate – Molecular and Cell Biology (Baylor College of Medicine)

Postdoctoral Fellow – Advanced Prostate Cancer Research (Cleveland Clinic)

Posdoctoral Position – Prostate Cancer Research (Louisiana State University Health Sciences Center)

Postdoctoral Fellow – Cancer Immunotherapy (University of Notre Dame)

Postdoctoral Fellow – Prostate Disease Research (Henry M. Jackson Foundation for the Advancement of Military Medicine)

Postdoctoral Position – Prostate Cancer (The University of Minnesota, Twin Cities)

Research Fellow – Prostate Cancer (Sechenov University)

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